The proposed project is designed to continue a systematic investigation of the hypothalamic mechanisms of body weight regulation and feeding. The present investigator has reported that lesions of the lateral hypothalamus chronically lower the level at which an animal regulates its body weight, and furthermore, that the feeding interruption produced by such lesions is a behavioral strategy for reducing body weight to this lower level. Since the hyperphagia associated with lesions of the ventromedial hypothalamus is also secondary to a weight regulation adjustment--an elevated weight level--our results led us to propose a body weight set point analysis of the two hypothalamic feeding syndromes. Additional work has supported this weight set-point hypothesis and suggested a variety of additional analyses. Put broadly, the aims of the research proposed in this renewal are (1) to identify the neural and the neuroendocrine pathways responsible for the altered body weight (or adipose tissue mass) set points associated with hypothalamic lesions, (2) to define more generally the pathway involved in the control of body weight through the use of rodent models that display regulatory extremes, and (3) to develop a taxonomy of the rodent models of obesity and altered weight regulation in terms of the particular neural and neuroendocrine mechanisms involved. Initially our investigation will focus on the use of surgical manipulations of rodents with perturbations of weight regulation in order to evaluate and extend several preliminary conclusions based on our recent research. These conclusions include the hypothesis that the hypothalamic weight regulation syndromes reflect lesion produced alterations in autonomic (vagal-splanchnic) tone maintained over visceral control of fat metabolism.